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Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions

Nature Immunology volume 4, pages 49–54 (2003) Cite this article

A Corrigendum to this article was published on 01 March 2003

Abstract

It has been proposed that HIV-1, in addition to directly infecting and killing CD4+ T cells, causes T cell dysfunction and T cell loss by chronic immune activation. We analyzed the effects of chronic immune activation in mice that constitutively expressed CD70, the ligand for the tumor necrosis factor receptor family member CD27, on B cells. CD70 transgenic (CD70 Tg) mice showed a progressive conversion of naive T cells into effector-memory cells, which culminated in the depletion of naive T cells from lymph nodes and spleen. T cell changes depended on continuous CD27-CD70 interactions and T cell antigen receptor stimulation. Despite this hyperactive immune system, CD70 Tg mice died aged 6–8 months from Pneumocystis carinii infection, a hallmark of T cell immunodeficiency. Thus, persistent delivery of costimulatory signals via CD27-CD70 interactions, as may occur during chronic active viral infections, can exhaust the T cell pool and is sufficient to induce lethal immunodeficiency.

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Figure 1: T cell proliferation in CD70 Tg mice.
The alternative text for this image may have been generated using AI.
Figure 2: T cell cellularity and phenotype in CD70 Tg mice.
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Figure 3: Requirements for enhanced T cell expansion and differentiation in CD70 Tg mice.
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Figure 4: Effector T cell phenotype of CD70 Tg mice is dependent on stimulation of the TCR by antigen.
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Figure 5: T cell characteristics of IFN-γ−/− × CD70 Tg mice.
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Figure 6: Clinical symptoms in CD70 Tg mice.
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Acknowledgements

We thank D. Kioussis (London, UK) for providing us with the F5 Tg mice and E. Eldering, J. Hamann, R. Lutter and K.A. Reedquist for critically reviewing the manuscript.

Author information

Author notes

  1. Kiki Tesselaar and Ramon Arens: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory for Experimental Immunology, Academic Medical Center, P.O. Box 22700, Amsterdam, 1100DD, The Netherlands

    Kiki Tesselaar, Ramon Arens, Paul A. Baars & René A.W. van Lier

  2. Department of Immunobiology, Sanquin/Research and Landsteiner Laboratory of the Academic Medical Center, Plesmanlaan 125, Amsterdam, 1066CX, The Netherlands

    Kiki Tesselaar, Ramon Arens, Gijs M.W. van Schijndel, Paul A. Baars & René A.W. van Lier

  3. Department of Hematology, Academic Medical Center, P.O. Box 22700, Amsterdam, 1100DD, The Netherlands

    Ramon Arens & Marinus H.J. van Oers

  4. Laboratory of Experimental Animal Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands

    Martin A. van der Valk

  5. Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands

    Jannie Borst

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  1. Kiki Tesselaar
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Correspondence to René A.W. van Lier.

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Tesselaar, K., Arens, R., van Schijndel, G. et al. Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat Immunol 4, 49–54 (2003). https://doi.org/10.1038/ni869

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